Organophosphorus (OP) pesticides are used extensively in agriculture throughout the world, and workers who apply pesticides range in age from children in their teens to adults in their 60s. There is compelling evidence that repeated low-level occupational and environmental pesticide exposures are associated with neurobehavioral performance deficits in adults. Adolescents working in agriculture are exposed to the same risks as adults but whether their risk is equivalent to or greater than that of adults is not known. Adolescents in Egypt are hired seasonally to apply pesticides to the cotton crop. The pesticide application to the cotton crop is highly regulated and standardized across Egypt, and is limited primarily to OP pesticides, primarily chlorpyrifos. This provides a unique opportunity to examine the impact of a highly consistent known OP pesticide exposure on the adolescent nervous system as measured by neurobehavioral tests. While we have preliminary evidence of exposures from dermal and urinary samples in adult Egyptian applicators and evidence of neurobehavioral deficits in adolescent applicators compared to controls, there is no quantitative exposure data available in adolescents. Furthermore, what is not established is if these exposure-related effects accumulate with repeated annual exposure (on summer jobs) and if such effects reverse after the exposure ends each year. The goal of this application is to examine the dose-related response of the adolescent nervous system to OP pesticides, to test the hypotheses that (1) repeated exposures produce a progressive deficit and (2) any deficit is reversible. In Aim 1, young applicators, adolescents 16 to 18 years old, will be studied across the pesticide application season to examine the effects of OP pesticide exposure (urinary metabolites, blood cholinesterase, and dermal patch [gauze] samples) on neurobehavioral performance. In Aim 2 we will strengthen and build the research capacity at Menoufia University through scientific training on research methods and measurement of effects, and a seminar series designed to foster grant-writing skills. Through the development of a follow-on R01 application we will propose to evaluate novel (more effective) biomarkers and develop an economical training intervention that can reduce exposures and thus any cumulative effects of pesticide exposure and the potential long-term effects of those exposures in adolescents in Egypt. PUBLIC HEALTH RELEVANCE: The goal of this application is to examine the dose-related response of the adolescent nervous system to organophosporus pesticides (OPs), to determine if repeated exposures produce a progressive deficit and to determine if this deficit is reversible. We propose to study the young applicators, adolescents 16 to 18 years old, across the pesticide application season and examine the effects of OP pesticide exposure (urinary metabolites, blood cholinesterase, and dermal patch [gauze] samples) on neurobehavioral performance. We will also expand the research capacity at Menoufia University and submit a follow-on R01 grant to develop an economical training intervention that can reduce exposures and thus substantially reduce the cumulative effects of pesticide exposure and the potential long-term effects of those exposures in adolescents in Egypt.